Hayley Jeal

Determination of the T cell epitopes of the lipocalin allergen, Rat n 1

Background Laboratory animal allergy (LAA) is an important cause of occupational sensitization and asthma. Rats are a frequent cause of LAA and the major rat allergen, Rat n 1, is a member of the lipocalin protein family, which includes several other animal allergens such as the cow allergen, Bos d 2. To date, Bos d 2 is the only mammalian lipocalin allergen to have been studied in detail.

Allergy to rodents: an update

Allergy to rodents in the workplace is an important occupational health problem affecting research, pharmaceutical and toxicological sectors and can have a serious impact on employees working in this area. Despite measures to reduce aeroallergen exposures to rodents in the workplace, there are few signs that this occupational health problem is declining. Rodent allergens are well characterized and exposure–response relationships have been demonstrated to be complex. More recently, the importance of rodent allergens outside of the workplace has been demonstrated in several studies of individuals with asthma. This review focuses on rodent allergy both in the workplace and in the home and examines the complex exposure–response relationships between allergen exposure and sensitization and asthma. Risk factors for rodent allergy and mechanisms of tolerance to rodent allergens are discussed.

Association of HLA class II alleles with sensitization to cow dander Bos d 2, an important occupational allergen

Allergic sensitization results from a complex interaction between genetic and environmental factors. Earlier studies have shown that highly polymorphic HLA genes are associated with a variety of allergies. Several important respiratory allergens belong to the family of lipocalin proteins. These include occupational sensitizers, such as cow Bos d 2 or rat Rat n 1, and prevalent indoor sensitizers, such as dog Can f 1 or cockroach Bla g 4. HLA associations with sensitization to lipocalin allergens are incompletely known. In the present study we have investigated an association between HLA alleles and sensitization to the major cow allergen Bos d 2. The HLA-DR/DQ genotypes of 40 Bos d 2-sensitized subjects having occupational asthma were determined by polymerase chain reaction (PCR) and the results were compared with the genotypes of 151 unrelated Finnish subjects. The frequencies of HLA class II alleles DRB1*0101, DRB1*0404, DQB1*0302, and DQB1*0501 were significantly higher among Bos d 2-sensitized than among control subjects. In addition, the allergic subjects expressed significantly lower frequencies of HLA-DRB1*0301 and DQB1*0201 alleles than did the control subjects. These data suggest that the HLA class II alleles DRB1*0101, DRB1*0404, DQB1*0302, and DQB1*0501, and the haplotypes that include them, are associated with sensitization to the major cow allergen Bos d 2, whereas HLA-DRB1*0301 and DQB1*0201 are dissociated with it. Amino acid analysis provides a biologically plausible explanation for the HLA associations.

Dual sensitization to rat and mouse urinary allergens reflects cross-reactive molecules rather than atopy

Background:  Sensitization to rats and mice can develop in laboratory animal workers exposed to only one species. Reasons for this dual sensitization are unclear but may reflect a genetic predisposition to developing allergy (atopy) or alternatively cross‐reactivity between rat and mouse urinary allergens. We examined cross‐reactivity between rat and mouse urine and the effect atopy has on dual sensitization in laboratory animal workers.

Respiratory protective equipment reduces occurrence of sensitization to laboratory animals

BACKGROUND Respiratory protective equipment (RPE) has been shown to reduce exposure to laboratory animal allergens, but there are no studies that have examined its effect on the development of sensitization. AIMS To examine the effect of RPE on the risk of sensitization to laboratory animals. METHODS Survey of UK laboratory animal workers conducted between 1999 and 2001. Information was recorded on the type of RPE used when first exposed to animals and at the time of the survey. Sensitization to rat urinary proteins was assessed using skin-prick tests and assays of specific serum IgE antibodies. RESULTS There were 776 workers surveyed of whom 228 had been exposed for fewer than 5 years. Those more recently employed were more likely to have used RPE. In employees with <5 years of exposure the use of face masks at first employment was associated with a lower prevalence of sensitization, irrespective of the intensity of exposure to laboratory animals. This reduction was significant only in those who entered the animal house daily. CONCLUSIONS The use of simple RPE at first exposure to laboratory animals may help to reduce the incidence of specific sensitization.

Epidemiology of laboratory animal allergy

Laboratory animal allergy is common and an important occupational health issue for the research, pharmaceutical and toxicological sectors. In most settings where there is regular contact with laboratory animals — chiefly small mammals — the prevalence of specific sensitisation is around 15% and the prevalence of clinical allergy around 10%. These figures probably underestimate the true risk of disease since epidemiological studies of the disease have been beset by response and survivor biases. Allergen exposure appears to be the most important modifiable risk factor, but the effects of such exposure seem to be modified importantly by individual susceptibility. Laboratory animal research shows no signs of becoming less common, and an increasingly susceptible (atopic) population is likely to be recruited into such work. Future studies should be designed to take into account the inherent biases of occupational epidemiology, to study in detail the immunological mechanisms that underlie sensitisation and tolerance, and to identify early biomarkers of each.

Association of maternal anti-HLA class II antibodies with protection from allergy in offspring

Recent studies have suggested that the birth order effect in allergy may be established during the prenatal period and that the protective effect may originate in the mother. HLA class II disparity between mother and foetus has been associated with significantly increased Th1 production. In this study, we investigated whether production of HLA antibodies 4 years after pregnancy with index child is associated with allergic outcomes in offspring at 8 years.

Isolation, Flow Cytometric Analysis, and Suppression Assay of CD4+ CD25+ T-Regulatory Cells

Allergy and asthma are characterized by airway hyperresponsiveness and chronic mucosal inflammation mediated by CD4+ Th2 lymphocytes and their cytokines. It is unclear why allergic individuals make a Th2-type T-cell response whereas other (non-allergic) individuals do not. Recently, attention has focused on regulatory mechanisms, such as T-regulatory cells, preventing IgE responses to allergens in nonatopic individuals. Regulatory CD4+CD25+ T cells have been described in both mice and humans. The suppressive phenotype of these cells has been associated with the expression of the forkhead transcription factor, Foxp3. It has been suggested that allergic disease may arise from an inappropriate balance between allergen activation of regulatory CD4+CD25+ T cells and effector Th2 cells or from the impairment in the suppressive activity of these so-called T-regulatory cells. The isolation of these T-regulatory cells is described in order to further our understanding of the role of these cells in allergic disease and asthma and allow us to design novel therapies.

Response by Meinir Jones and Hayley Jeal

We wish to comment on the paper published online ‘‘Jeal H, Jones M. Allergy to rodents: an update. Clin Exp Allergy 2010; 40: 1593-601’’. The recent article of Jeal and Jones is interesting, particularly because it shows very well that allergy to rodents is still an important health problem both in the workplace and in the home despite an increasing knowledge of the disease in the last few decades [1]. However, we believe that in the Summary the sentence ‘‘there are few signs that this occupational health problem is declining’’ is misleading as the evidence for this statement is lacking. On the contrary, in our review, which included 15 cross-sectional studies, there was the suggestion of a progressive decline in the prevalence of occupational asthma due laboratory animals, which was estimated as 4.0% from 1977 to 2001 [2]. Of course, the observations of our study are open to discussion and may even be rejected but they should not be disregarded.